Method and an apparatus for treating tumoral diseases (cancer)

ABSTRACT

An apparatus ( 40 ) according to the invention includes a radiation emitter ( 34 ) for ionizing radiation and a high voltage generator ( 1 ) for generating brief voltage pulses for voltage application of electrodes ( 6, 15, 16, 24 ) included in the apparatus. The electrodes are designed to be secured at or introduced into tissue in a restricted region of a human or an animal and to form between them an electric field in the tissue. The radiation emitter ( 34 ) is provided to emit ionizing radiation to a tumor in the tissue in that region which is to be treated, while the electrodes ( 6, 15, 16, 24 ) are disposed to be placed in or at the tumor in order that the electric field pass through the tumor.

FIELD OF INVENTION

The present invention relates to a method and an apparatus forgenerating pulses of electric fields in a resricted area of a human oran animal, according to the preambles to the independent claims.

BACKGROUND OF INVENTION

The forms of therapy which are routinely applied in modern medicine fortumoral therapy often fail to achieve local tumor control, which is thecause of death of roughly 30% of cancer patients. It is, therefore,important to develop novel and improved techniques for local andregional tumor treatment.

In today's medical care, radiation therapy, also known as radiationtreatment, surgery and combinations hereof are the most commonlyemployed methods for treating malignant tumors. Roughly every secondpatient suffering from infiltrating cancer is treated by radiationtherapy, but only roughly half of these patients are cured. Such failuredepends, on the one hand, on the presence of a wider spread disease(distant metastasis) or recurrence (a regrowth of a tumor in thetreatment region), and, on the other hand, because certain tumor formsare resistant to radiation.

Attempts have been made, with varying success, to reinforce and improvethe efficiency of radiation therapy in sterilizing tumors. For example,use has been made of more sophisticated radiation therapy techniques,such as stereotactic treatment, “conformal radiotherapy” of changedfractioning or added medication to increase the radiation sensitivity inthe tumors.

Use is also made of heat as adjuvant to ionizing radiation which, forcertain tumor forms, may increase the number of complete remissions byup to a factor of two.

It is obvious that there are both desires and needs in the art for amore efficient technique for treating tumors.

SUMMARY OF INVENTION

The characterizing clauses of the independent claims disclose atechnique which entails a substantial improvement of the efficiency ofthe radiation therapy in sterilizing tumors.

The present invention relates to an apparatus which includes means forsubjecting a tumor in a human or in an animal to one or more pulses ofan electric field with a field strength adjustable for the pertinenttreatment field, and means for ionizing radiation treatment of thetumor.

The present invention also relates to a method of treating tumors by acombination of ionizing irradiation and of pulses of electric fieldswhich, in the tumor, have a field strength exceeding a predeterminedlevel.

Expedient embodiments of the present invention are further disclosed inthe appended subclaims.

In the application of the present invention, it has proved that thesurvival of tumor cells has been reduced substantially if they are firsttreated with ionizing radiation and thereafter exposed to pulses ofelectric fields with an electric field strength exceeding a certainlevel. This survival has fallen by a factor of 10 compared with survivalin exclusively ionizing radiation. The tumors in rats have completelydisappeared when they were treated with a combination of ionizingradiation and electric fields with a field strength exceeding a certainlevel.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention will be described in greater detail below withreference to a number of figures, in which:

FIG. 1 shows the results of an experiment conducted on Jan. 11-15, 1996;

FIGS. 2a-c show photographs of a tumor in a rat;

FIG. 3 shows the mean value of tumor size as a percentage of the initialsize in tumors according to FIG. 2;

FIG. 4 is a block diagram showing a schematic apparatus for applying anelectric field and/or ionizing radiation in a resricted region of ahuman or an animal;

FIG. 5 is a block diagram of one embodiment of a combination of meansfor the generation of electric fields in a resricted region in a humanor an animal;

FIG. 6a-d show embodiments of electrode applicators for externaltreatment of tumors;

FIG. 7 shows one embodiment of an electrode applicator for intraoperative treatment of tumors and for the treatment of superficial tumornodules;

FIGS. 8a-d show embodiments of electrodes and electrode applicatorsdesigned for the interstitial treatment of tumors;

FIG. 9a-c show embodiments of electrodes and electrode applicatorsdesigned for the treatment of tumors in body cavities and in organsaccessible via large vessels;

FIG. 10 shows embodiment of the electrodes in which these are designedfor combination treatment with antitumoral medication; and

FIGS. 11a-e show examples of forms of voltage pulses applied to theelectrodes.

DETAILED DESCRIPTION

FIG. 1 shows, in a bar chart, the result of an experiment which wasconducted on Jan. 11-15, 1996. Fibroblast cells (V79-cells) in 7 groupsof small plastic tubes were placed in the experiment, in a water bathand were irradiated with ionizing radiation to a radiation absorbed doseof 2 Gy. ⁶⁰Co gamma radiation was employed for the irradiation.

Within two hours, the V79-cells were exposed, in 6 of the groups, to asequence of 8 brief (1 ms) pulses of electric fields of high electricfield strength which passed through the cells. The electric fields weregenerated by electric high voltage pulses. The sequences of the electricfields applied to the cells in each one of the groups at differentpoints in time after the ⁶⁰Co gamma radiation. The high voltage pulseswere of exponential form with a time constant of 1 ms and of anamplitude which generated an electric field with a maximum fieldstrength corresponding to approx. 1600 V/cm through the cells. Thepulses were repeated at 1 s intervals.

FIG. 1 show the outcome of the treatments of the V79-cells described inthe two preceding paragraphs. The X-axis shows “time in minutes betweenthe ⁶⁰Co gamma radiation and the high voltage pulses”, and the Y-axisshows the “percentage surviving cells”. The first bar in the histogramshows the survival of cells after radiation treatment alone. With onlythis treatment, roughly 55% of the cells survived. The remaining bars inthe bar chart show the survival when the ⁶⁰Co gamma radiation wascombined with the pulses of electric fields. When the pulses wereapplied within two hours from the ⁶⁰Co gamma radiation, survival levelfell to a mean count of less than approximately 10%.

The combination of radiation treatment of tumors and the generation ofelectric fields through them will, hereinafter, be designated as a rule“electrodynamic radiation therapy” or “electrodynamic radiationtreatment”. This expression is employed regardless of whether theradiation treatment precedes the treatment with electric fields, whetherthe radiation treatment takes place after the treatment with electricfields or whether the two treatments wholly or partly overlap oneanother.

FIG. 2 and FIG. 3 show the results of an animal experiment with tumorcells implanted in the leg flank of rats. After approx. 3 weeks,palpable tumors developed. The tumors were treated daily for 4 days (May21-24, 1996), partly with ⁶⁰Co gamma radiation alone to an absorbed doseof 2 Gy, and partly with electrodynamic radiation treatment with (2Gy+16 pulses of field strength approx 1300 V/cm in the tumor).

FIG. 2a shows a photograph of an untreated tumor in a rat, FIG. 2b showsa photograph of a tumor in a rat 47 days after radiation treatment ofthe tumor with 4×2 Gy ⁶⁰Co gamma radiation, and FIG. 2c shows aphotograph of a rat 47 days after electrodynamic radiation treatment ofthe tumor: 4×(2 Gy+16 electric pulses approx. 1300 V/cm, 1 ms, 1 s⁻¹).With electrodynamic radiation treatment, no palpable tumor remains. Thetreatments with the electric fields were conducted each time after theradiation treatment and within one (1) hour.

FIG. 3 shows the mean value of “tumor size as a percentage of initialsize” (the Y-axis), partly after solely radiation treatment <3> with⁶⁰Co gamma radiation 4×2 Gy, and partly after electrodynamic radiationtreatment <4>, with 4× (2 Gy+16 pulses at approx. 1300 V/cm in thetumor). The measurement points show the mean value of the tumor size for4 conventionally radiation treated <3> and 3 electrodynamicallyradiation treated rats, respectively, <4> at different times in daysafter the treatment (the X-axis) Also in this experiment, treatment withelectric fields took place after the radiation treatment.

The mean value of tumor size at different points in time after thetreatment for 4 radiation <3> and 3 electrodynamically radiation treated<4> rats, respectively, with tumors shows that the tumors treated withelectrodynamically radiation treatment disappeared rapidly and withoutany recurrence or regrowth, while only conventional radiation treatmentgives a partial reduction of the tumor size, with continued tumor growthafter approx. 3 weeks.

It is obvious that, in radiation treatment of tumoral diseases, theeffect of the treatment is reinforced by combining the radiationtreatment of the tumors with short intensive pulses of electric fieldsthrough the tumors. Experiments conducted indicate that, for certaintypes of tumors, the treatment with electric fields should be conductedbefore the radiation treatment, while for other types the treatment withelectric fields and radiation treatment should wholly or partly overlapone another.

Examples of ionizing radiation suitable for combination with an electricfield through the tumor are:

1. Gamma radiation and electron radiation from encapsulated radioactivepreparations (e.g. ⁶⁰Co, ¹³⁷Cs, ²²⁶Ra, ¹⁹²Ir, etc.),

2. Photon radiation from X-ray tubes and linear accelerators;

3. Electron radiation from accelerators (10 keV−50 MeV);

4. Proton radiation, heavy ions, neutrons;

5. Radiation from applied or injected radioactive isotopes, so-calledradioactive medicines (alpha, beta, gamma radiation, auger electrons,conversion electrons and characteristic X-ray radiation; and

6. Neutron radiation from nuclear reactors used in neutron capturetherapy (in, for example,boron reactions so-called BNCT

It may be ascertained that, as a rule, an improvement will be obtainedof the treatment result in irradiation of tumors with ionizing radiationin combination with the tumors also being exposed to electric fields ofa field strength exceeding a certain level. This applies regardless ofthe employed type of ionizing radiation.

FIG. 4 shows the present invention with the aid of a block diagram. Theschematically illustrated apparatus 40 shown in the Figure comprises ahigh voltage generator 1, a radiation emitter 34 and electrodes6,15,16,24 As a rule, a registration and conversion device 10 is alsoincluded in the apparatus, for example a computer or a microprocessor10. Hereinafter, the word computer will generally be employed for theregistration and conversion device, without any restrictive intent.Between the high voltage generator 1 and the electrodes 6,15,16,24,there is provided one or more signal communications 32 and electricleads 33. In those embodiments where the computer 10 is included, thereare provided signal communications 32 between the computer and theelectrodes 6,15,16,24 and the radiation emitter 35. While the signalcommunications 32 in the Figure are shown as directly connecting thecomputer and the electrodes, it will be obvious to a person skilled inthe art that the apparatus as such also includes devices considered inthe continuation of this description, such as switches 3, distributorunits 4, electrode applicators 5, etc. for controlling the voltageapplication of the electrodes and/or activation and deactivation ofionizing radiation, etc.

FIG. 5 schematically shows one embodiment of a combination of means forgenerating electric fields in an apparatus according to the invention.In the Figure, blocks are shown for a high voltage generator 1, acapacitor battery 2, a switch 3, a distributor unit 4 for distributionof high voltage pulses generated on discharge of the capacitor battery 2through the switch 3 to an electrode applicator 5 and electrodes 6intended to be placed in or adjacent a tumor 7. The high voltagegenerator 1, the capacitor battery 2, the switch 3 and the distributorunit 4 are, by means of electric leads 33, connected in series to oneanother. Between the distributor unit 4 and the electrode applicator 5,there are provided at least one electric lead 32 and at least one signalcommunication 32. Via the signal communication 32, the distributor unit4 controls the voltage application of the electrodes of the electrodeapplicator which, via the electric leads 33 are inter-connected with thedistributor unit 4 and, via the electric lead 33, to the switch 3. Inone alternative embodiment, each electrode 6 is electrically connectedto the switch 3 by an electric lead 33.

As a rule, the switch 3 or the electrode applicator applies voltagesimultaneously only to two electrodes 6, while other electrodes arepermitted to assume that potential which is determined by the placing ofthe electrode in the treatment region. The term voltage application alsoencompasses, in this context, the feature that one or more electrodesare earthed (have zero potential). The switch 3 and/or the electrodeapplicator 5 are disposed, if desired, to permit pairwise voltageapplication of all electrodes which are applied in the treatment region.It will be obvious to a person skilled in the art, that, in certainembodiment, these means provided, on voltage application, to allocate toseveral electrodes a substantially corresponding potential.

Via signal communications, all units are connected to a registration andconversion device 10, also designated computer 10. The computer 10constitutes a control and monitoring device for the function of theapparatus.

The expression electrode applicator 5 signifies a retainer for theelectrodes 6, the retainer being designed so as to facilitate thecorrect application of the electrodes to or in the treatment region.

The computer is set generally for the high voltage pulses to include thefollowing data:

repetition frequency approx. 0.1-10 pulses/second amplitude approx.500-6000 V pulse length approx. 0.1-2 ms number of pulses 5-20 pertreatment.

The pulses are applied before, during or just after the radiationtreatment. Examples of employed pulse forms are square pulses with apulse length of 0.1-2 ms or exponentially fading pulses with a timeconstant RC approximately equal to 0.1-2 ms.

In embodiments in which the high voltage generator 1 emits modulatedA.C. voltage at high frequency, approx. 40-100 kHz use is made of amodulator instead of capacitor battery and switch so as to form brief,modulated high frequency pulses of a pulse length within the range ofbetween approx. 0.1 and 10 ms.

As will be apparent from the embodiment illustrated in FIG. 5, theapparatus generally also includes sensors 8 intended to be applied tothe patient in the treatment region. The sensors are connected via adetector interface 9 to the registration and conversion device 10. Onapplication of the treatment pulse, a signal is generated in the sensors8 which, via the interface 9, is transferred to and registered in thecomputer 10. From the signals measured, the computer calculates theelectric field strength induced by the pulse and the electromotoricforce in different parts of the treatment region 7. These signals entailthat the computer 10 emits signals to the high voltagegenerator/capacitor battery (feedback connection) to adjust theamplitude of the generated pulses such that the predetermined fieldstrength is attained in the treatment region. This monitoring andadjustment takes place continuously during the application of thepulses.

FIGS. 6a-d show embodiments of electrode applicators 5 for the externaltreatment of a tumor, with the electrodes 6 applied in a resrictedregion to the patient and in different configurations around the tumor7. FIGS. 6a and 6 b show how, by cruciform application of the electrichigh voltage pulses to different combinations of two electrodes 6, itwill be achieved that, as marked in the Figure by the electric fieldforce lines, the electric field passes through all parts of the tumor 7.

FIGS. 6c-d show how electrodes are designed with abutment surfaces ofdifferent sizes in order that the field lines be focused to the desiredtreatment region. Electric high voltage pulses whose voltage is adjustedin response to the distance between the electrodes are applied during,immediately before or after the radiation treatment. The voltage isadjusted in accordance with the relationship:

Voltage=(constant)×(the distance between the pairwise electrodes).

The value of the constant is varied in dependence upon the type of tumorand is selected as a rule to values of between approx. 500 and 3000V/cm.

FIG. 7 shows one embodiment of an electrode applicator 5 forintra-operative treatment and treatment of superficial tumor nodules 7.The electrode applicator has scissor-shaped formation and comprises twoshanks 12 of electrically insulating material (e.g. Teflon™) which aremovably interconnected to one another in a journal 11. The shanks areprovided with a gripping block 13. At one end of each shank 12, theshanks are provided with finger grips and, at the other ends, withelectrodes 6 which grasp about the tumor nodules 7. The gripping block13 fixes the shanks 12 in the set position. The voltage of the electrichigh voltage pulses is adjusted in response to the size of the tumor 7with the aid of a distance sensor 14 integrated in the electrodeapplicator and connected to the computer 10. The voltage is determinedin accordance with the relationship:

Voltage=(constant)×(the distance between the pairwise electrodes).

The value of the constant is adapted in response to the type of tumorand is generally selected within the range of between approx. 500 and3000 V/cm.

FIGS. 8a-d show embodiments of electrodes 15,16 and a fixture 18 for theelectrodes, in which the electrodes and the fixture are suitable to beemployed for interstitial treatment of both superficial and profoundtumors. In FIG. 8a, the electrode 15,16 are shown in two differentembodiments, namely in one embodiment in which the electrodes 15 areneedle-shaped, and one embodiment in which the electrodes 16 arestiletto-shaped, and one embodiment in which the electrodes 16 arestiletto-shaped. Each one of the electrodes 15,16 is provided, in aregion 31 most proximal their one end, with an electric conductor 32 forconnection to the high voltage generator 1. The above-mentioned portionis provided with an electrically insulating layer 17 or an electricallyinsulating sleeve 17 in which the electrode is inserted.

The electrodes are applied in different configurations in and about thetumor 7, either directly by free hand, or with the aid of a perforatedelectrode applicator (fixture) 18. The electrode applicator is generallydesigned to be removed from the electrodes 15,16 once these have beenapplied to the patient. It will thereby become possible to allow theelectrode to remain in position in the patient in order to be employedon several subsequent treatment occasions. Alternatively, the electrodeapplicator is removed together with the electrodes 15,16 after eachtreatment. Also in interstitial treatment, electrodes with surfaces ofdifferent sizes occur for controlling the extent of the electric field.

The parts of the electrodes 15,16 which are intended to be placed in thepatient in order to cover the extent of the tumor 7 are, for example,manufactured from stainless steel of a quality which tallies with orcorresponds to that employed for injection syringes, or are manufacturedfrom other tissue-friendly metal such as noble metal.

The remaining portion of the electrodes forms a insulated portion 17with leads 33 for the high voltage pulses. In the employment of soft,flexible leads, the electrodes is placed in a large calibre cannula 19which, after application of the electrodes in the patient, is withdrawn,the electrodes remaining in position in the tissue.

In certain embodiments, the electrodes consist of radioactive metal(e.g. iridium 192, cobalt 60) or are surface-coated with radioactivesubstances (e.g. iodine 125). In other embodiments, they are designed astubes 20 of inert metal which are charged with radioactive material(e.g. ¹⁹²Ir, ¹³⁷Cs, ²²⁶Ra) which ideally takes place using a so-calledafter charge apparatus 22. Electric voltage pulses are supplied to theelectrodes in the treatment region before, during or immediately afterthe radiation treatment. The pulses have a voltage which is determinedby the distance between the electrodes. The voltage is set in accordancewith the relationship:

Voltage=(constant)×(the distance between pairwise electrodes).

The value of the constant is selected in dependence upon the type oftumor, as a rule within the range of between approx. 500 and 3000 V/cm.

FIGS. 9a-c show electrodes 24 for the treatment of tumors in livingorgans accessible via, for example, large vessels, or bodily cavities,for example respiratory tracts, urinary tracts or the intestinal tract.The electrodes are disposed on the surface of a cylinder-like electrodeapplicator 23 of insulating material. In certain embodiments, theelectrodes are designed such that they are passed into the tissuethrough channels 25 in the applicator 23, operated by a remote control.As is apparent from FIG. 9c, the embodiment of the channel 25 disclosedin the previous sentence discharges in the circumferential surface ofthe electrode applicator, whereby the electrodes 24, on theirdisplacement, are guided into tissue which surrounds the electrodeapplicator. In certain embodiments, the applicator is disposed to besupplied with radioactive preparations, whereby the applicator alsoforms a radiation device. The applicator is disposed to be supplied withthe radioactive preparation manually, or by means of an after chargedevice 22. Electric high voltage pulses whose voltage is adjusted inresponse to the distance between the electrodes are applied before,during or immediately after the radiation treatment, in accordance withthe relationship:

Voltage=(constant)×(the distance between pairwise electrodes).

The value of the constant depends upon the type of tumor. As a rule, thevalue of the constant is selected within the range of approx. 500 to3000 V/cm.

The field lines in FIG. 9a indicate the extent of the electric fieldlines in the tissues.

For intracavital treatment of tumors in different, irregularly shapedbodily cavities (e.g. the oral cavity, respiratory tract, oesophagus,stomach, uterus, bladder, urether, rectum) electrode applicators 23 are,as is apparent from FIGS. 9a-c, applied specifically designed inaccordance with the configuration of the cavity with electrodes appliedon the surface 24, or alternatively designed as needles which are passedinto the tissue through ducts 25 by remote control. These applicatorsare suitable to be used, for example, for the treatment of lung cancer,liver tumors, renal tumors and tumors in the intestinal tract withreduced absorbed dose in order to reduce the side effects of radiationtreatment in normal tissues. Prostate cancer is treated with applicatorsapplied via the rectum and urether. These applicators are, in certainembodiments, designed to be charged with radioactive sources orradioactive material 21, either manually or by an after charge device22.

Electric high voltage pulses whose voltage is adjusted in response tothe distance between the electrodes are applied before, during orimmediately after the radiation treatment. The voltage is adjusted inaccordance with the relationship:

Voltage=(constant)×(the distance between pairwise electrodes).

The value of the constant is varied in dependence upon the type of tumorand is generally selected between approx. 500 and 3000 V/cm.

FIG. 10 shows an apparatus for the combination treatment withantitumoral medication, in which the electrode 6 is coated with a layer28 of porous metal, glass, ceramics, inert plastic or other polymerwhich contains antitumoral medication 29 (e.g. bleomycin, platinol,taxol, monoclonal antibodies), genetic material (chromosomes, DNA), orradioactive substances (e.g. iodine 125, auger electron emitters). Thistype of electrode is well suited to be used in electrodynamic radiationtherapy, since the high electric field strength increases thepermeability of the tumor cells for the above-mentioned substances andthereby increases the antitumoral effect.

FIGS. 11a-e show examples of pulse forms in the voltage pulses which arepairwise applied to the electrodes 6,15,16,24. In the Figures, theheight of the pulses represents the voltage between two electrodes. Thewidth of the pulses represents the length of the pulse. FIGS. 11a and 11c show examples of square pulses, FIG. 11b and 11 d show examples ofpulses whose voltage fades with time, and FIG. 11e shows pulses of A.C.voltage. FIGS. 11c and 11 d show voltage pulses in which, analogous withthat which applies to A.C. voltage, the electrodes alternatively havethe highest voltage, whereby a corresponding change takes place of theelectric field between the electrodes.

In one realization of the present invention, the radiation emitter andthe electrodes in certain embodiments together with the electrodeapplicator form a combined mechanical unit. This is of a design whichmake it possible, in a restricted region of a human or an animal, toapply both the radiation emitter and the electrodes in positions wherethe ionized radiation is directed towards the tumor and in which theelectrodes have positions in which electric fields between them passthrough the tumor. In other embodiments, these means constitute separatemechanical parts which, together, and where applicable, over time, forma system of means and devices of a composition corresponding to thatdisclosed above for the apparatus 40.

The present invention should not be considered as restricted to thatdescribed above and shown on the Drawings, many modifications beingconceivable without departing from the scope of the appended Claims.

What is claimed is:
 1. An apparatus (40) comprising a high voltagegenerator (1) for generating brief voltage pulses for voltageapplication of electrodes (6,15,16,24) included in the apparatus, orelectrodes (6,15,16,24) connected to the apparatus, the apparatusincluding means (4,5) for distributing the voltage pulses to theelectrodes (6,15,16,24) characterized in that the apparatus alsoincludes means (34) for supplying ionized radiation to a tumor (7)existing in a human or in an animal, that the electrodes (6,15,16,24)are designed to be secured to a resricted region of the human or theanimal, or designed to be inserted in said region in order, on treatmentof the tumor, to form therebetween electric fields, that the fields havea field strength which exceeds a predetermined level, and that theelectrodes are disposed, in the treatment, to be placed in or at thetumor (7) in positions entailing that the electric field passes throughthe tumor.
 2. The apparatus as claimed in claim 1, characterized in thatthe apparatus includes sensors (8) for detecting electric fields formedby the electrodes (6,15,16,24), and that the sensors are connected to aregistration and conversion device (10) for calculating the size of theelectric field strength in the treatment region and, for regulating theamplitude of the voltage pulses applied to the electrodes, theregistration and conversion device (10) is connected to the high voltagegenerator (1) and/or to means (2,3,4) connected in between the highvoltage generator (1) and the electrodes (6,15,16,24).
 3. The apparatusas claimed in claim 1, characterized in that the electrodes (6) aredisposed to be excited alternatingly and only two at a time.
 4. Theapparatus as claimed in claim 1, characterized in that the apparatusincludes sensors (14) for detecting the distance between the electrodes(6) in each pair of excited electrodes, and that the registration andconversion device (10) includes means for adjusting the voltage betweenthe electrodes (6) in each pair of excited electrodes based on thedistance between the electrodes.
 5. The apparatus as claimed in claim 1,characterized in that the electrodes (6) are designed as needles (15) orstilettos (16).
 6. The apparatus as claimed in claim 1, characterized inthat the electrodes (6,15,16,24) are wholly surrounded by anelectronically insulating layer (17) or have an electrically insulatinglayer which at least leaves an electrically conductive tip of theelectrodes uninsulated.
 7. The apparatus as claimed in claim 1,characterized in that an electrode applicator (5,23) is disposed for atleast temporarily fixing the electrodes prior to placing of theelectrodes on or in the treatment region.
 8. The apparatus as claimed inclaim 7, characterized in that the electrode applicator (23) is of asize and configuration which are adapted to the vessel, body aperture orbodily cavity where it is to be placed.
 9. The apparatus as claimed inclaim 7, characterized in that the electrode applicator (5) includes afixture (18) for fixing the electrodes (15,16) in a fixed pattern. 10.The apparatus as claimed in claim 7, characterized in that the fixture(18) is provided with a number of holes for placing the electrodes in adesired pattern on each treatment occasion.
 11. The apparatus as claimedin claim 1, characterized in that the apparatus includes at least onecannula (19) each one provided for temporarily enclosing an electrode.12. The apparatus as claimed in claim 1, characterized in that theelectrodes (6,15,16,24) consist of radioactive material or are designedwith cavities for accommodating radioactive preparations (21).
 13. Theapparatus as claimed in claim 1, characterized in that the electrodes(6,15,16,24) are coated with a layer (27) of porous material forabsorbing therapeutic substances (28).
 14. The apparatus as claimed inclaim 8, characterized in that the electrode applicator (23) is providedwith electrodes (24) placed on the surface of the applicator, or thatthe electrodes (24) are placed in ducts (25) discharging in apertures inthe surface of the applicator and displaceable by remote control in theducts, and at least partly out through the apertures in order to bepassed into the tissue surrounding the applicator.
 15. A method ofexposing a resricted region of a human or an animal to a treatmentcomprising generation of electric fields through tissue within therestricted region, characterized in that the treatment with electricfields is combined with a treatment by means of ionizing radiation, andthat the treatment with the ionizing radiation takes place within alimited interval in time prior to or after the treatment with electricfields or in a time interval within which the treatment with electricfields and ionizing radiation wholly or partly overlap one another. 16.The method as claimed in claim 15, characterized in that the treatmentis employed for sterilizing tumors.